Dynamics of muscle microcirculatory and blood-myocyte O(2) flux during contractions.

The O(2) requirements of contracting skeletal muscle may increase 100-fold above rest. In 1919, August Krogh's brilliant insights recognized the capillary as the principal site for this increased blood-myocyte O(2) flux. Based on the premise that most capillaries did not sustain RBC flux at rest, Krogh proposed that capillary recruitment [i.e. initiation of red blood cell (RBC) flux in previously non-flowing capillaries] increased the capillary surface area available for O(2) flux and reduced mean capillary-to-mitochondrial diffusion distances. More modern experimental approaches reveal that most muscle capillaries may support RBC flux at rest. Thus, rather than contraction-induced capillary recruitment per se, increased RBC flux and haematocrit within already-flowing capillaries probably elevate perfusive and diffusive O(2) conductances and hence blood-myocyte O(2) flux. Additional surface area for O(2) exchange is recruited but, crucially, this may occur along the length of already-flowing capillaries (i.e. longitudinal recruitment). Today, the capillary is still considered the principal site for O(2) and substrate delivery to contracting skeletal muscle. Indeed, the presence of very low intramyocyte O(2) partial pressures (PO(2)s) and the absence of intramyocyte PO(2) gradients, whilst refuting the relevance of diffusion distances, place an even greater importance on capillary hemodynamics. This emergent picture calls for a paradigm-shift in our understanding of the function of capillaries by de-emphasizing de novo'capillary recruitment'. Diseases such as heart failure impair blood-myocyte O(2) flux, in part, by decreasing the proportion of RBC-flowing capillaries. Knowledge of capillary function in healthy muscle is requisite for identification of pathology and efficient design of therapeutic treatments.

Effects of combined aging and heart failure on visceral sympathetic nerve and cardiovascular responses to progressive hyperthermia in F344 rats.

Sympathetic nerve discharge (SND) responses to hyperthermia are attenuated in aged rats without heart failure (HF) and in young HF (Y(HF)) rats, demonstrating that individually aging and HF alter SND regulation. However, the combined effects of aging and HF on SND regulation to heat stress are unknown, despite the high prevalence of HF in aged individuals. We hypothesized that SND responses to heating would be additive when aging and HF are combined, demonstrated by marked reductions in SND and mean arterial pressure (MAP) responses to heating in aged HF (A(HF)) compared with aged sham HF (A(SHAM)) rats, and in A(HF) compared with Y(HF) rats. Renal and splenic SND responses to hyperthermia (colonic temperature increased to 41.5°C) were determined in anesthetized Y(HF), young sham (Y(SHAM)), A(HF), and A(SHAM) Fischer rats. HF was induced by myocardial infarction and documented using echocardiographic, invasive, and postmortem measures. The severity of HF was similar in Y(HF) and A(HF) rats. SND responses to heating were attenuated in Y(HF) compared with Y(SHAM) rats, demonstrating an effect of HF on SND regulation in young rats. In contrast, A(HF) and A(SHAM) rats demonstrated similar SND responses to heating, suggesting a prominent influence of age on SND regulation in A(HF) rats. Splenic SND and MAP responses to heating were similar in Y(HF), A(HF), and A(SHAM) rats, indicating that the imposition of HF in young rats changes the regulatory status of these variables to one consistent with aged rats. These data suggest that the effect of HF on SND regulation to hyperthermia is age dependent.

Effects of altering pedal frequency on the slow component of pulmonary VO2 kinetics and EMG activity.

This study investigated the effects of pedal frequency on the slow component of pulmonary oxygen uptake ( V O(2)) kinetics during heavy exercise at the same relative intensity. We hypothesized that higher pedal frequency (expected to enhance fast-twitch muscle fiber recruitment) would be associated with greater slow component amplitude (A' (s)), surface electromyography (normalized root mean square; RMS) and blood lactate concentration ([lactate]). Eight subjects performed square-wave transitions to heavy exercise at 35 and 115 rpm. Furthermore, alternated cadences square-wave transitions (35-115 rpm) were performed to examine the potential effects of additional fast-twitch muscle fiber recruitment on the slow component. Significance was accepted when P<0.05. The A' (s) was greater at higher cadences (0.58+/-0.08 and 0.70+/-0.09 L.min (-1) at 115 and 35-115 rpm, respectively) than at 35 rpm (0.35+/-0.04 L.min (-1)). Greater EMG increase over time (DeltaRMS ((10-3 min))) and [lactate] were observed at 115 and 35-115 rpm compared with 35 rpm. There was a significant correlation between A' (s) and overall DeltaRMS ((10-3 min)) for all pedal frequencies combined (r=0.63; P=0.001). Pedal frequency had no effect on time constants or time delays. These findings are consistent with the concept that progressive recruitment of muscle fibers is associated with the V O(2) slow component.

Nitric oxide bioavailability modulates the dynamics of microvascular oxygen exchange during recovery from contractions.

AIM: lowered microvascular PO(2) (PO(2) mv) during the exercise off-transient likely impairs muscle metabolic recovery and limits the capacity to perform repetitive tasks. The current investigation explored the impact of altered nitric oxide (NO) bioavailability on PO(2) mv during recovery from contractions in healthy skeletal muscle. We hypothesized that increased NO bioavailability (sodium nitroprusside: SNP) would enhance PO(2) mv and speed its recovery kinetics while decreased NO bioavailability (l-nitro arginine methyl ester: l-NAME) would reduce PO(2) mv and slow its recovery kinetics. METHODS: PO(2) mv was measured by phosphorescence quenching during transitions (rest-1 Hz twitch-contractions for 3 min-recovery) in the spinotrapezius muscle of Sprague-Dawley rats under SNP (300 microm), Krebs-Henseleit (CONTROL) and l-NAME (1.5 mm) superfusion conditions. RESULTS: relative to recovery in CONTROL, SNP resulted in greater overall microvascular oxygenation as assessed by the area under the PO(2) mv curve (PO(2 AREA) ; CONTROL: 3471 ± 292 mmHg s; SNP: 4307 ± 282 mmHg s; P < 0.05) and faster off-kinetics as evidenced by the mean response time (MRToff; CONTROL: 60.2 ± 6.9 s; SNP: 34.8 ± 5.7 s; P < 0.05), whereas l-NAME produced lower PO(2 AREA) (2339 ± 444 mmHg s; P < 0.05) and slower MRToff (86.6 ± 14.5s; P < 0.05). CONCLUSION: no bioavailability plays a key role in determining the matching of O(2) delivery-to-O(2) uptake and thus the upstream O(2) pressure driving capillary-myocyte O(2) flux (i.e. PO(2) mv) following cessation of contractions in healthy skeletal muscle. Additionally, these data support a mechanistic link between reduced NO bioavailability and prolonged muscle metabolic recovery commonly observed in ageing and diseased populations.

Effects of gender and aerobic fitness on cardiac autonomic responses to head-up tilt in healthy adolescents.

Cardiovascular autonomic responses to orthostatic challenges are affected by gender and cardiorespiratory fitness in adults. However, little is know about the effects of these factors in healthy adolescents. We studied 41 adolescents (20 boys and 21 girls) aged 12-17 years, divided into aerobic fitness tertiles based on the results of a maximal treadmill exercise test. Cardiac autonomic modulation was assessed by heart rate variability (HRV) analysis of 5-minute RR interval recordings before and after 70 degrees head-up tilt maneuver. HRV was analyzed by time (TD) and frequency domain (FD) methods. TD was analyzed by standard deviation of the RR intervals and the root mean square of successive differences of RR intervals. The power spectral components were studied at low (LF) and high (HF) frequencies and as the LF/HF ratio. We did not find any differences in TD and FD measures before and after tilt in either gender or fitness groups, except for a higher heart rate response for boys. These results suggests that cardiac autonomic responses to head-up tilt in healthy adolescents are not affected by gender or aerobic fitness.